Immunotherapy compositions and methods
a composition and immunotherapy technology, applied in the field of universal immunotherapy compositions, can solve the problems of difficult identification, difficult and costly to generate a tcr or antibody that recognizes tumor neoantigens for each patient, and only modest success of car t cell therapy against solid tumors
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example 1
lize Tumor Targeted Antibodies with Masked Small Molecules
[0241]The goal of this example is to construct a scaffold consisting of a backbone structure polymer structure coupled to small molecules, which can be further modified with a protease sensitive hydrogel polymer. PEG is a good choice for functionalizing the small molecules scaffold because it stabilizes biomolecules, it is resistant to degradation and the coupling chemistries are established. Any number of small molecules can be chosen. This scaffold of PEG / small molecule / protease sensitive hydrogel polymer will be coupled to a tumor targeted antibody.
example 2
lize Tumor Targeted Antibodies with Masked Small Molecules
[0242]The goal this example is to use a Probody® CytomX technology which uses protease sensitive peptides to block the tumor targeting antibody's ability to recognize its antigen. In this strategy the small molecule is expected to be directly coupled to the Fc portion of the antibody or to some other site outside of the antigen recognition portion of the antibody. We will select the small molecule based on its pharmacological activity.
example 3
of a pH-Dependent Polymer to Unmask Small Molecules Only in Proximity of a Tumor
[0243]The general strategy for this technology is development of a peptide whose conformation is altered in a pH dependent fashion. We plan to covalently link small molecules antigens to this peptide. Under physiologic conditions, the peptide will fold back on itself to mask the small molecule. Under acidic conditions, the peptide will open, unmasking the small molecules. The advantage of the strategy is that antibodies not bound to the tumor will mask the small molecules blocking inappropriate and unintended activation of the immune system. The general strategy for linking the hydrogel polymer to the tumor targeting antibody in Phase I will be adapted to linking this peptide to the tumor-targeting antibody. As alternative strategy, this pH-sensitive peptide can be directly injected into a tumor to generate an immune response.
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